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Call for ContributionsHETEROCYCLES Special Issue Vol. 99 in honor of Professor Tohru Fukuyama on 70th Birthday

Submission deadline: September 10, 2018
On the occasion of Professor Tohru Fukuyama's 70th birthday, HETEROCYCLES editorial office is planning to publish special anniversary issue on April 1, 2019 as Vol. 99. Authors are invited to submit their work to this topical issue.
Authors wishing to submit their manuscript should contact editorial office via e-mail by the end of May, 2018. Manuscript should reach the editorial office no later than September 10, 2018.
Contact: submit@heterocycles.com

March 5, 2018

Heterocycles Award
HETEROCYCLES is pleased to announce Heterocycles Award.
In recognition of an outstanding oral presentation at the 47th Congress of Heterocyclic ChemistrySee more

December 13, 2017

Call for ContributionsHETEROCYCLES Special Issue Vol. 97 in honor of Professor Kiyoshi Tomioka on 70th Birthday

Submission deadline: February 15, 2018
On the occasion of Professor Kiyoshi Tomioka's 70th birthday, HETEROCYCLES editorial office is planning to publish special anniversary issue on September 1, 2018 as Vol. 97. Authors are invited to submit their work to this topical issue.
Authors wishing to submit their manuscript should contact editorial office via e-mail by the end of November, 2017. Manuscript should reach the editorial office no later than February 15, 2018.
Contact: submit@heterocycles.com

Abstract

Methylation of the title compounds (10-S-3 sulfurane: 1-3) took place exclusively on the nitrogen at 3(4)-position and selectively on the nitrogen bound to the more electron-withdrawing heterocycle. The activation energy of the hindered rotation in 5 was lower for the pyrimidine ring (DGc≠ = 20.2 kcal mol-1) bound to the methylated nitrogen than the other one (DGc≠ = 22.9 kcal mol-1).

■ Application of Electro-Oxidative α-Cyanation of Aza-Rings to the Synthesis of Gephyrotoxin 223AB

Abstract

Six and five-membered cyclic α-cyanoamines have been prepared efficiently from N-benzylpiperidine and N-benzylpyrrolidine. These α-cyanoamines were successfully used in the synthesis of gephyrotoxin 223AB

Abstract

A short and convergent synthesis of pyrrolophenanthridone alkaloids, such as anhydrolycorin-7-one, oxoassoanine, hippadine, and pratosine, was developed by using directed lithiation and palladium-catalyzed corss-coupling as key reactions. Anhydrolycorin-7-one was converted to an antitumor alkaloid, kalbretorine, via directed lithiation and hydroxylation reactions.

Abstract

The photolyses of the γ-allenyl-substituted conjugated alkylidenecycloalkanones underwent the intramolecular oxa-Diels-Alder reaction and the E-Z geometrical isomerization, and for the cyclopentanone possessing a 3-methyl-1,2-butadienyl group, the intramolecular [2+2] cycloaddition also occurred. The oxa-Diels-Alder reaction takes place via photochemical process of the Z-enones.

■ New Transformation of Lactam Sulfides to Tetrahydro-3,6-epithiobenzazocines via Bicyclic Sulfonium Salts with a Sulfonio Bridgehead

Abstract

Benzothiazinone (1) was chlorinated with N-chlorosuccinimide and subsequently submitted to [2++4] cycloaddition with 1,3-dienes in the presence of silver perchlorate to afford cyclic sulfonium salts (3). Reactions of 3 with sodium borohydride or sodium hydride provided 4-vinyltetrahydro-3,6-epithiobenzazocine derivatives (9) in good yields.

Abstract

The high reactivity of [1,2,4]thiadiazolo[2,3-a]pyridinium salts against electrophiles is described. This fact provides a new and efficient synthetic route to several heterocycles such as thiazolines, thiadiazolines and thiadiazoline-3-ones carrying pyridylimino substituents.

Abstract

The absolute stereochemistry of the Ophiorrhiza alkaloid ophiorrhizine has been defined as shown in formula [(-)-1] by a chemical correlation with the Cinchona alkaloid cinchonine through cincholoipon ethyl ester [(+)-3] and the lactim ether [(+)-2]. The correlation was achieved by the chiral synthesis of ophiorrhizine [(-)-1] from (+)-2via the intermediates [(+)-5], [(+)-7],[(+)-6], (8), [(-)-9], [(-)-10], (11), [(-)-12], and [(-)-13].

Abstract

The addition of allyltriphenylstannane to 3-sulfinylfurfural (3) in the presence of titanium(IV) tetrachloride proceeded with high diastereoselectivity to give the furyl alcohol (6), whereas the similar treatment with tin(IV) tetrachloride afforded the other diastereoisomeric alcohol (7), exclusively.

■ Nuclear Magnetic Resonance Studies of Hyaluronan (HA): Evidence of Competitive Inhibition of Interchain Associations by Phospholipids which may result in decreased Anti-Inflammatory and Cartilage Protecting Properties of HA

Peter Ghosh,* Nongporn Hutadilok, and Aldo Lentini

*Raymond Purves Bone & Joint Research Laboratories, The Royal North Shore Hospital of Sydney, University of Sydney, St. Leonards, NSW 2065, Australia

Abstract

The chain flexibility of solutions of hyaluronan (HA) of different molecular weights was determined by 1H-nmr spectroscopy in the absence and presence of the phospholipid Dipalmitoyl DL-α-phosphatidylchline (DPC). Sonication of high or low molecular weight HA with DPC for periods up to 60 min markedly increased HA chain flexibility as determined by observing the spin-spin relaxation times for the glucosamine acetyl group protons. From these data it is proposed that DPC competes for those hydrophobic centres along the HA chain which are normally responsible for the inter and intra chain interactions and which confer stiffiness to the HA molecule.

Abstract

N-[2-(Phenylsulfinylmethyl)phenyl]pyrrole (4) undergoes transfer sulfenylation to N-(2-chloromethylphenyl)-2-phenylthiopyrrole (5‘) presumably viaS-phneyl 5H-pyrrolo[1,2-a][3,1]benzothiazonium chloride (7). Depending upon the rigor of the reaction conditions, either N-(2-hydroxymethylphenyl)-2-phenylthiopyrrole (5) or its 5-trifluoroacetyl derivative (6) are obtained when 4 is treated with TFAA in trifluoroacetic acid. N-[2-(Methylsulfinylmethyl)aryl]pyrroles (12), when treated with gaseous hydrogen chloride and the resulting sulfonium salts refluxed in dichloroethane, produce substituted 5H-pyrrolo[1,2-a][3,1]benzothiazines (14). 1-Formyl-5H-pyrrolo[1,2-a][3,1]benzothiazines (22) are formed in one step in good yield when sulfoxides (12) are reacted with the Vilsmeier-Haack reagent (DMF/POCl3). No Pummerer rearrangement product is isolated from these reactions.

Abstract

Vilsmeier formylation of 4-methyloxazole (1) gave a mixture of 4-methyl-5-oxazolecarboxaldehyde (2) and 4-methyl-2-oxazolecarboxaldehyde (3) in 1:1 ratio. Both aldehydes were prepared unambiguously: aldehyde (2) by oxidation of 5-hydroxymethyl-4-methyloxazole (4) and reduction of chloride of 4-methyl-5-oxazolecarboxylic acid (5) and aldehyde (3) by n-butyllithium/DMF procedure. Aldehyde (2) sublimes in a refrigerator while aldehyde (3) forms hydrate, 5-dihydroxymethyl-4-methyloxazole (8).

Abstract

The pyridazino[4,5-b]indole (3), which is conveniently available from 3-methylthioindole and the tetrazine (2), undergoes thermally induced inverse-electron-demand Diels-Alder reactions with enamines to afford the cycloalkene-annelated carbazoles (7,8) or the 2-substituted carbazole (9), respectively.

Abstract

Members of two novel families of spiro(oxazolidinediones) have been prepared. Spiro[1H-isoindole-1,5‘-oxazolidine]-2‘,3(2H),4‘-triones (4) were synthesized from the corresponding 1-hydroxy-1-carboxyethylisoindol-3-one (7) or (10) or their primary amide derivatives (14). In turn 7 and 10 were prepared from 2-bromobenzoic acid amides (6) and (9), or from N-alkylated isoquinolin-1,3,4(2H)-triones (12). Spiro[1,2-benzisothiazole-3(2H),5‘-oxazolidine]-2‘,4‘-dione 1,1-dioxides (5) were constructed from the appropriate 2,3-dihydro-3-hydroxy-1,2-benzisothiazole-3-carboxamide 1,1-dioxide (17). The immediate precursors to 14, ethyl esters (16) and (19), were prepared from benzenesulfonamide (15), or from 2-bromobenzenesulfonamide (18).

■ A New Entry to 5-Unsubstituted 3-Acyltetramic Acids from Aldehydes

Abstract

Reaction of aldehydes (prim-, sec-, and tert-) with diazoacetamide (8, 9) of N-substituted glycinate in the presence of Zr(IV) chloride in CH2Cl2 affords β-keto amides (11, 12) in good to high yields, which on treatment with n-Bu4NF in THF are led to N-protected 3-acyltetramic acids (13, 14).

Abstract

The title compound (8) was prepared by a [4+2] cycloaddition reaction of 3,6-bis(trifluoromethyl)-1,2,4,5-tetrazine (1) with a 4-piperidone-derived enamine and subsequent aromatization of the tetrahydro compound (7). The azadiene reactivity of 8 was investigated employing enamines and a ketene-N,S-acetal as electron-rich dienophiles. A series of new condensed isoquinolines (10, 11, 12a,b, 13) was obtained and one of them (13) was characterized by X-ray structure determination.

Abstract

Reactions of chloromethyl aryl ketoximes (1, X = Cl) with tetrasulfur tetranitride in p-dioxane at reflux for 4 h afforded 3-aryl-1,2,5-thiadiazoles (2) in 37-92% yields, whereas those of bromo analogs under the same conditions gave 2 and 3-aryl-4-bromo-1,2,5-thiadiazoles (3) in 48-81% and 17-31% yields, respectively. However, the compounds (3) were not formed in the presence of pyridine. α-Nitrosostyrene and its ring-substituted derivatives (4) are proposed as intermediates for the formations of 2.

Abstract

Reactions of pyrazolo[1,5-a]pyridines with Eschenmoser‘s salt, activated alkenes and alkynes, and chlorosulfonyl isocyanate provided general routes to 3-substituted pyrazolo[1,5-a]pyridines such as 3-dimethylaminomethyl- and 3-(2-nitroethyl)pyrazolo[1,5-a]pyridines, 1-phenyl-3-(pyrazolo[1,5-a]pyrid-3-yl)-2-propen-1-ones, 4-(pyrazolo[1,5-a]pyrid-3-yl)-3-buten-2-one, pyrazolo[1,5-a]pyridine-3-carboxamide, and pyrazolo[1,5-a]pyridine-3-carbonitrile.

■ EPC-Synthesis of (S)-3-Hydroxy-3-mercaptomethylquinuclidine, a Chiral Building Block for the Synthesis of the Muscarinic Agonist AF 102B

Abstract

The catalytic modification of the Sharpless-epoxidation reaction was employed in a short EPC-synthesis of the title compound. The asymmetric epoxidation of the allylic alcohol (6) proceeded in 75 % yield and 94 % enantiomeric excess. In a 4 step sequence the epoxide (7) was transformed to (S)-3-hydroxy-3-mercaptomethylquinuclidine (11).

*Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmacal Sciences, Purdue University, 1333 Robert E. Heine Pharmacy Building West Lafayette IN 47907, Indiana 47907, U.S.A.

Abstract

Two new highly cytotoxic adjacent bis-tetrahydrofuran acetogenins, bullatin (2) (10-hydroxy-4-deoxybullatacin) and bullanin (5) (30-hydroxy-4-deoxybullatacin), have been isolated from the ethanolic extract of the stem bark of Asimina triloba by directing the fractionation with brine shrimp lethality. In addition to these two new compounds, two previously reported acetogenins, squamocin (3) (28-hydroxy-4-deoxybullatacin) and motrilin (4) (29-hydroxy-4-deoxybullatacin) which are new to this species, were obtained. Through spectral analysis these four acetogenins were structurally identified as hydroxylation isomers of bullatacin (1) which was recently patented as an antitumor agent. All of these acetogenins showed high potencies in the brine shrimp test (BST) and in cytotoxicity tests against human solid tumor cell lines in culture, with certain potencies quite comparable to those of bullatacin (1) and several orders of magnitude greater than those of adriamycin.

■ Unexpected Results in the Reduction of Tetracyclic Enamides. Structure, Stereochemistry and Conformation of a 20β-Hydroperoxyimine

Abstract

Reduction of Nb-allyl-20-ethyltetracyclic enamide (7) with lithium aluminium hydride afforded the expected enamine (12) and 4a-oxoethylhexahydrocarbazolones (18a,b). Reduction of Nb-unsubstituted enamide (6), under the same conditions, gave imine (9), enamine (11) and a 20β-hydroperoxytetracyclic imine (19) resulting from the peroxydation of 9 and 11. The C-20 stereochemistry of 19 was established by means of 2D 1H nmr and NOE difference spectroscopy.

Abstract

A novel 6-aryl-1,2-benzopyran derivative named garcipyran was isolated from the roots of Garcinia kola (Guttiferae) and the structure was elucidated by spectroscopic and chemical methods. The plausible biogenetic pathways of 6-aryl-1,2-benzopyran (garcipyran) and 5-arylbenzofuran (garcifuran-B) were also discussed.

■ A New Sesquiterpene Lactone Glucoside of Ixeris chinensis

Abstract

A new sesquiterpene lactone glucoside, 8-epicrepioside G(1) together with two known compounds, 8-epidesacylcynaropicrin glucoisde (2) and ixerin D (3) were isolated from the whole plant of Ixeris chinensis. Their structures were determined on the basis of chemical and spectroscopic evidence. Compounds 1, 2 and 3 taste of strong bitterness.

Abstract

Three new acridone-coumarin dimers, named dioxinoacrimarine-A (1), neoacrimarine-E (2) and acrimarine-N (3) were isolated from the roots of Citrus plant and their structures were elucidated on the basis of spectroscopic methods.